Responsive Layout is my new favourite field of specialization. Given how many pages are still not optimized for mobile (including the one you are just reading, but not for much longer), there is a lot to do. And since responsive has not been around so very long, it often feels quite exploratory. I like to fool myself into believing I just solved an problem unsolved before. That is not true of course, but at least you have not read about the solutions so often.
Making a design responsive can be done on multiple levels. Until now I have done mostly basic stuff. To really rock the socks one surely should do a seperate layout for mobile instead of creating a beautiful desktop layout and just make it "not-too-ugly" on mobile. This is in my plans for future sites I build and design for sure. For now, I am quite happy doing the not-too-ugly thing.
Once you feel you got a foothold in mediaqueries and mobile-first responsive layout (which is the way to go, I think), other things pop up. Your average slideshow on the frontpage can be just hidden for mobile, which sure is not ideal. Building a touch-enabled slideshow is on TODO list. Slideshows are hard anyway, since often the div-container and image size properties are intertwined. I did not manage yet to make my favourite weapon Views Slideshow smoothly scale the image with the screen-size, so I won't touch upon that.